Inner Ear 21 

The cochlea is a conical cavity in the petrous portion of the temporal bone which contains the organ of Corti. The role of the cochlea is not limited to the transduction of fluid vibrations into nerve impulses; it also includes the frequency analysis of these vibrations before they are transmitted to the central auditory structures. Fluid vibrations in the cochlea are initiated by the movement of the stapes footplate in the oval window. These vibrations activate the release of neurotransmitter into the synaptic clefts at the base of the hair cells, which propagate auditory nerve impulses. The frequency analysis of these fluid vibrations is related to the mechanical properties (i.e., the stiffness gradient) of the basilar membrane (BM), and the active metabolic mechanisms of the outer hair cells (OHCs), both of which help to optimally activate different frequency regions of the BM.

The earliest embryological sign of the development of the cochlea is the thickening of the cephalic ectoderm--the otic placode. The otic placode invaginates into the mesenchymal tissue by the fourth week of fetal development to form the otic pit. As the invaginated portion of the otic pit enlarges, the mouth narrows until the two sides merge forming a closed sac--the otic otocyst (Altmann, 1950; Bast & Anson, 1949; O’Rahilly, 1963; Wong, 1983). The epithelium of the otic otocyst gives rise to the primary neurons of the vestibulocochlear ganglion. These ganglions later divide into superior (i.e., vestibular ganglion supplying the common macula) and inferior (i.e., spiral ganglion supplying sensory hair cells) branches (Pearson, et al., 1973) late in the fourth or early in the fifth week GA. After invagination, the otic otocyst divides into the endolymphatic duct and sac, the utricle, semicircular canals and the saccule, as well as the cochlear duct (Altmann, 1950; Bast & Anson, 1949; Bredberg, 1968; Pearson et al., 1973; Wong, 1983). Thus, by the six week GA the sensory epithelium of the otic otocyst divides into vestibular and cochlear regions, into which terminal nerve fibers from the vestibulocochlear ganglia will grow.

While various changes are taking place in the otic otocyst, the mesoderm surrounding it is also undergoing development. Consequently, toward the end of the sixth week GA, the condensed mesenchyme tissue completes its transformation to cartilage at the peripheral areas of the developing otic otocyst. During the course of the next two weeks the organ of Corti develops in the wall of the cochlear duct, its inner ridge (later known as the spiral limbus) and outer ridge (later differentiates into the organ of Corti) are already noticeable. Both ridges secrete a jelly- like substance forming the nascent tectorial membrane. A highly vascularized band of cells (stria vascularis) begins to develop on the outer wall of the cochlear duct in the eighth week GA. Just one week later, nerve fibers from the spiral ganglion are seen entering the epithelium below

the posterior wall (i.e., BM) of the cochlear duct (Pearson et al., 1973; Pujol & Lavigne- Rebillard, 1985; Wong, 1983). Late in the seventh week GA the cochlear duct completes one turn around the modiolus, and continues to course spirally around the modiolus two and one half turns by the ninth week GA (Pearson et al., 1973; Pujol & Lavigne-Rebillard, 1985). The developing tectorial membrane covered in the organ of Corti’s primordium is detected by the 10th week GA (Pujol, Lavigne-Rebillard, & Uziel, 1991).

As morphological development of the otic otocyst proceeds, the epithelium covering the BM starts to exhibit signs of maturation beginning in the basal end proceeding gradually toward the apex. Afferent nerve fibers begin to invade the undifferentiated cochlear epithelium--with a slight developmental precedence of inner hair cells (IHCs) over that of OHCs (Anson & Donaldson, 1981; Bast & Anson, 1949; Bredberg, Engstrom, & Ades, 1965; Bredberg, 1967, 1968; Lavigne-Rebillard & Pujol, 1986, 1988). In the 11th week GA, the cochlear duct (i.e., scala media) begins to differentiate. Perilymphatic spaces begin to change the cross-sectional form of the cochlear duct from rounded to triangular--the posterior wall formed by the BM, the anterior wall by the vestibular (Reissner's) membrane, and the outer wall formed by the spiral ligament and the bony lamina--separating the three spirally-running scalae which communicate at the apex of the cochlea (Anson & Donaldson, 1981; Bast & Anson, 1949; Bredberg, 1968).

Subsequently, the differentiation of stereocilia bundles begins on the IHCs first, then the OHCs in the 12th week GA. The first vesiculated efferent endings are visible below the IHCs in the 14th _{week, contrasting with the late arrival of synapses between the medial}

efferent endings and the OHCs around the 20th week GA (Lavigne-Rebillard & Pujol, 1988; Pujol & Lavigne-Rebillard, 1985). All rows of inner and OHCs are apparent by the 14th week

GA and their characteristic arrangement of stereocilia is seen around the 22nd week GA (Lavigne-Rebillard & Pujol, 1986, 1988; Pujol & Lavigne-Rebillard, 1985; Pujol et al., 1991). As soon as the staircase arrangement of stereocilia becomes clear, tip links are present on most of the hair cells (Lavigne-Rebillard & Pujol, 1986). By the 16th week GA auditory nerve fibers are present in all turns of the cochlea and are tonotopically distributed; the center contains nerve fibers arising from the apex and the outer covering contains nerve fibers from progressively more basal regions of the cochlea (Rubel, 1978). Between the 20th and the 22nd week GA, the inner and outer ridges from the epithelial cells of the scala media form the spiral limbus and the organ of Corti, respectively. At the same time, the stria vascularis is well developed forming a thick covering over the entire outer wall (Bredberg, 1968). Simultaneously appearing is the opening of the tunnel of Corti, the formation of Nuel’s spaces, the elongation of the outer pillars, and the development of divergent cell types (i.e., Deiters’ cells, Hensen’s cells) (Altmann, 1950; Lavigne-Rebillard & Pujol, 1986, 1988; Pujol & Lavigne-Rebillard, 1985).

By the 23rd week GA all the ossification centers of the otic otocyst have fused to form a completely bony capsule. Just one week later, the organ of Corti is present in all turns of the cochlea, and the last stages regarding the formation of synapses, as well as the formation of cilia are almost complete (Pujol & Lavigne-Rebillard, 1985). Functional maturation of the cochlea is attained by the 25th week GA (Anson & Donaldson, 1981; Bast & Anson, 1949). Outer HCs, Deiters’ cells and other surrounding cochlear structures reach maturity slightly after the onset of cochlear function, by the 30th week GA (Lavigne-Rebillard & Pujol, 1990; Pujol & Uziel, 1988).

In summary, the myriad of structural events that synchronously occur prenatally, harmoniously contribute to the formation and onset of auditory function (cf. Table 1). Even though, anatomic maturity of the ME and the cochlea of the IE is not completely attained

25

prenatally, unconditional fetal auditory responsiveness (e.g., limb and body movements, heart rate and eye blink) occurs as early as the 25th week GA (Birnholz & Benacerraf, 1983; Crade & Lovett, 1988; Johansson, Wedenberg, & Westin, 1963), and reliable components of evoked potentials can be successfully recorded around the 27th week GA (Galambos & Hecox, 1978; Rotteveel, de Graaf, Colon, Stegeman, & Visco, 1987a; Starr et al., 1977).

While this chapter subsection addressed the development of the peripheral auditory structures, subsection 3.3 will detail the functional roles and salient points involving human formation and growth of the central auditory system.

Table 1 Embryonic Development of the Peripheral Auditory System

GAa Middle Ear Inner ear

3rd

Marks the start of the primitive formation of the tympanic cavity and eustachian tube, and the anlage for the auditory ossicles, muscles, tendons and connective tissues. Trigeminal and facial nerves connect through the chorda tympani.

4 _{The otic placode invaginates to form the otic otocyst.} 5

The vestibulocochlear ganglion divides into superior and inferior branches and the sensory epithelium of the otic otocyst divides onto the vestibular and cochlear regions.

6

The auditory ossicles are visible.

The peripheral areas of the otic otocyst transform to cartilage. Marks the beginning of the formation of the organ or Corti, the spiral limbus and the tectorial membrane.

7

The cochlear duct completes one turn around the modiolus. 8

The primordium of the manubrium of the malleus becomes defined.

The stria vascularis begins to develop on the outer wall of the cochlear duct.

9 Condensed connective tissue forms the tympanic membrane. The _{eustachian tube and the tympanic cavity proper are realized.}

Nerve fibers from the spiral ganglion enter the epithelium below BM. The cochlear duct completes two and one half turns around the modiolus.

10

The external auditory meatus becomes apparent and the formation of the tegman tympani occurs. In the same week the pars tensa of the tympanic membrane becomes visible.

The developing tectorial membrane is detected. The epithelium covering the BM starts to mature basal-to-apex. Afferent nerve fibers being to invade the cochlear epithelium, first the IHC then the OHCs.

11 _{The anlage of the stapedius muscle becomes defined. The cochlear duct begins to differentiate.} 12 The facial canal is realized. The malleus and the incus begin to

change to precartilage.

Differentiation of stereocilia bundles begins on the IHCs then the OHCs.

13 _{The tensor tympani is actualized.}

14 The stapes begins to change to true cartilage.

Efferent endings are visible below the IHCs. All rows of inner and OHCs are apparent.

27

Table 1 continued.

16

Ossicles have attained maximum size. Bone formation is initiated in the malleus and incus.

Nerve fibers are present in all turns of the cochlea and are tonotopically distributed.

19 Ossification begins in the stapes.

20 The pars flaccida of the tympanic membrane becomes visible.

Synapses between the medial efferent endings and the OHCs are apparent.

21

The spiral limbus and the organ of Corti form. The stria vascularis is well developed. The opening of the tunnel of Corti, the formation of Nuel’s spaces, the elongation of the outer pillars, and the

development of divergent cells types start to appear. 22

Staircase arrangement of stereocilia becomes clear and tip links are present.

23

The anterior and lateral walls of the tympanic cavity develop and the tympanic antrum forms. The tegman tympani start to ossify.

All ossification centers have fused to form a completely bony capsule.

24

The organ of Corti is present on all turns of the cochlea. The formation of cilia is almost complete.

25

The round window, tympanic sinus and a large part of the oval window form. Tympanic cavity widens.

Functional maturation of the cochlea and unconditional fetal auditory responsiveness is attained.

27 Reliable components of AEPs can be successfully recorded. 28

Pneumatization of the temporal bone occurs; the deposition of the petrous and mastoid bones continues through childhood.

29

Pneumatization of the epitympanic recess and the tympanic cavity occurs.

30

Outer HCs, Deiters’ cells and other surrounding cochlear structures reach maturity.

32

Ossification of the malleus and incus is complete; stapes continues until adulthood.

36 The epitympanic recess and the tympanic cavity are pneumatized. 40 The formation of the tympanic membrane is fully developed. Note: a _{Weeks of gestation.}